Washington — The Senate is going through a brain drain, of sorts, with two senators leaving to take the top spots in the White House, two more leaving to join the cabinet, and then an assortment leaving through retirement and defeat – including the longest continuously serving Republican senator in history.

Turnover, of course, is normal, but this year there’s a twist: both the new president and vice president are leaping straight from the Senate. The last time that happened was in 1960, with John F. Kennedy and Lyndon Johnson. Then add the two senators who have been nominated to join President-elect Obama’s Cabinet – Hillary Rodham Clinton as secretary of State and Ken Salazar as Interior secretary. Usually, just one senator gets plucked for a new cabinet, notes associate Senate historian Donald Ritchie.

With a big, aggressive agenda in the works as soon as Mr. Obama is inaugurated, congressional observers expect all this inside knowledge of Capitol Hill – enhanced by Rep. Rahm Emanuel’s soon-to-be role as White House chief of staff – will help pave the way to get legislation passed. Another House member, Rep. Hilda Solis (D) of California, is expected to get the Labor secretary job.

“They’ll have a lot of intel in the White House about what the feeling is up here,” says a Senate staffer. “So it probably redounds to both institutions to have this much cross-pollination.”

Under one-party Democratic rule, the administration will for the most part set the agenda, but Congress will be needed to pass the legislation. In the House, where the Democratic majority will be larger come January, the rules make it easier than in the Senate for the majority to dominate. In the Senate, 60 votes out of 100 are required to halt debate, and the Democrats fell short of that total.

Not that holding 60 seats would have guaranteed anything for the Democrats, in any event, as some senators regularly don’t move in lock step with their caucus.

In addition, George Voinovich of Ohio and Arlen Specter of Pennsylvania remain as possible aisle-jumpers, depending on the issue. A first-term Republican senator who has emerged as someone willing to work the middle is Tennessee’s Bob Corker. He won bipartisan praise in his efforts to reach a deal on auto bailout legislation, which ultimately failed.

Things could also get tricky on the Democratic side. Soon-to-be Vice President Joseph Biden, a 36-year veteran of the Senate from Delaware, will not be welcome at the Senate Democratic caucus’s weekly meetings, majority leader Harry Reid of Nevada has pronounced. And there are plenty of centrist Democrats in the Senate, particularly from the South and Mountain West, who could stray from the party fold on some issues.

First-term Senator Salazar of Colorado is one Democrat who was known for working the middle with regularity. He was a member of the bipartisan “Gang of 14” senators who fought to keep the judicial nomination process from blowing up, and he also played the center on immigration. Now, as the nominee for Interior, some fans of the legislative branch are sorry to see Salazar leaving the Capitol. And there’s no guarantee that Colorado, a battleground state, will keep that seat Democratic in the 2010 election.

On balance, though, Colorado is better off with Salazar at Interior, given the outsize importance of land and water issues in the state, says Denver-based independent pollster Floyd Ciruli.

All the other brain power and institutional memory leaving the Senate represents the normal changing of the guard that goes with an institution whose membership evolves over time. The departure of Sen. Ted Stevens of Alaska, convicted of corruption and then (barely) voted out of office last month, represents the end of an era, funneling countless federal dollars to Alaska’s benefit over 40 years.

In the next Congress, the 111th, there will be 31 first-term senators – not an extraordinary proportion of newbies, according to Mr. Ritchie, the historian. And furthermore, says Ross Baker, a political scientist at Rutgers University, the Senate is organized with a lot of redundancy in mind.

“The Senate, to a very great extent, runs on the wisdom of staff, both personal staff and committee staff,” says Mr. Baker, who has worked in the Senate during sabbaticals. “They really go a long way to tiding the Senate over in times of turnover like this.... It’s an institution that has withstood a lot more than this.”